tbuckley/cabot-search huggingface dataset:
Association of High-Dose Erythropoietin With Circulating Biomarkers and Neurodevelopmental Outcomes Among Neonates With Hypoxic Ischemic Encephalopathy
Authors: Sandra E. Juul, Emily Voldal, Bryan A. Comstock, An N. Massaro, Theo K. Bammler, Dennis E. Mayock, Patrick J. Heagerty, Yvonne W. Wu, Adam L. Numis, Kaashif Ahmad, Mariana Baserga, Ellen Bendel-Stenzel, Kristen Benninger, Lina Chalak, Taeun Chang, John Flibotte, Fernando Gonzalez, Andrea Lampland, Nathalie Maitre, Amit Mathur, Stephanie Merhar, Ulrike Mietzsch, Brenda Poindexter, Rakesh Rao, David Riley, Christopher Smyser, Gregory Sokol, Krisa Van Meurs, Joern-Hendrik Weitkamp, Tai-Wei Wu, Toby Yanowitz
Journal: JAMA Network Open (2023)

The ability to predict neurodevelopmental impairment (NDI) for infants diagnosed with hypoxic ischemic encephalopathy (HIE) is important for parental guidance and clinical treatment as well as for stratification of patients for future neurotherapeutic studies.
Displays of 18F-FAPI PET/CT in Myocarditis With Variable Symptom Durations
Authors: Weicheng Zhou, Jinju Sun, Fangyang Wang, Yi Wang, Xiao Chen
Journal: Clinical Nuclear Medicine (2023)

We report cardiac 18 F-FAPI PET/CT findings in 3 cases with myocarditis of varying duration (7 hours, 1 week, and 1 month). Myocarditis with varying symptom durations showed different 18 F-FAPI uptake, suggesting that the 18 F-FAPI PET/CT may be helpful in evaluating the extent of fibrosis caused by myocarditis. This information may assist in treatment decision-making for patients with myocarditis.
Identifying p53 Target Genes Using Hypomorphic Variants
Authors: Bibek Bhatta, Tomer Cooks
Journal: Cancer Discovery (2023)

Summary: The reduced tumor suppression activity of hypomorphic variants of the TP53 gene was used by Indeglia and colleagues to corroborate PADI4 as a p53 target. The study makes a noteworthy advancement in comprehending the downstream implications of TP53–PDI4, including potential predictions of survival and the efficacy of immunotherapy. See related article by Indeglia et al., p. 1696 (4).
Major adverse cardiovascular events in patients with atopic dermatitis treated with oral Janus kinase inhibitors: a systematic review and meta-analysis
Authors: Cécile Ertus, Lucie-Marie Scailteux, Alain Lescoat, Pauline Berthe, Vincent Auffret, Alain Dupuy, Emmanuel Oger, Catherine Droitcourt
Journal: British Journal of Dermatology (2023)

Abstract Background On the basis of safety data for patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors (JAKi) has been linked to the occurrence of major adverse cardiovascular events (MACE). However, these inflammatory diseases are proatherogenic; in contrast, patients with atopic dermatitis (AD) do not usually have a high cardiovascular (CV) comorbidity burden. Objectives To perform a systematic review and meta-analysis of MACE in patients with AD treated with JAKi. Methods We systematically searched PubMed, Embase, Cochrane Library and Google Scholar from their inception to 2 September 2022. Cohort studies, randomized controlled trials and pooled safety analyses providing CV safety data on patients taking JAKi for AD were selected. We included patients aged ≥ 12 years. We built a ‘controlled-period’ cohort (n = 9309; 6000 exposed to JAKi and 3309 exposed to comparators) and an ‘all-JAKi’ cohort (n = 9118 patients exposed to a JAKi in any of the included studies). The primary outcome was a composite of acute coronary syndrome (ACS), ischaemic stroke and CV death. The broader secondary MACE outcome encompassed ACS, stroke (whether ischaemic or haemorrhagic), transient ischaemic attack and CV death. The frequency of primary and secondary MACE was assessed in both cohorts. A fixed-effects meta-analysis using the Peto method was used to calculate the odds ratio (OR) for MACE in the ‘controlled-period’ cohort. Evaluation of the risk of bias was done using the Cochrane risk-of-bias tool (version 2). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Eight per cent of the records identified initially met the selection criteria, corresponding to 23 records included in the ‘all-JAKi’ cohort. Patients had been exposed to baricitinib, upadacitinib, abrocitinib, ivarmacitinib, placebo or dupilumab. Four primary events (three with JAKi and one with placebo) and five secondary events (four with JAKi and one with placebo) occurred among 9309 patients in the ‘controlled-period’ cohort (MACE frequency 0.04% and 0.05%, respectively). Eight primary events and 13 secondary events occurred among 9118 patients in the ‘all-JAKi’ cohort (MACE frequency 0.08% and 0.14%, respectively). The OR for primary MACE in patients with AD treated with JAKi vs. placebo or dupilumab was 1.35 (95% confidence interval 0.15–12.21; I 2 = 12%, very low certainty of evidence). Conclusions Our review highlights rare cases of MACE among JAKi users for AD. JAKi may have little-to-no effect on the occurrence of MACE in patients with AD vs. comparators, but the evidence is uncertain. Real-life long-term population-level safety studies are needed.
National Assessment of Pediatric Readiness of US Emergency Departments During the COVID-19 Pandemic
Authors: Katherine E. Remick, Hilary A. Hewes, Michael Ely, Patricia Schmuhl, Rachel Crady, Lawrence J. Cook, Lorah Ludwig, Marianne Gausche-Hill
Journal: JAMA Network Open (2023)

The National Pediatric Readiness Project assessment provides a comprehensive evaluation of the readiness of US emergency departments (EDs) to care for children. Increased pediatric readiness has been shown to improve survival for children with critical illness and injury.
Modeling the Landscape of Histone-Mutant Pediatric High-Grade Gliomas: A Study in Partner Alterations
Authors: Evan Lubanszky, Cynthia Hawkins
Journal: Cancer Discovery (2023)

Summary: Pediatric high-grade gliomas represent a group of deadly, heterogeneous tumors, often driven by histone mutations and the accumulation of clonal mutations, correlating with different tumor types, locations, and age of onset. In this study, McNicholas and colleagues present 16 in vivo models of histone-driven gliomas to investigate subtype-specific tumor biology and treatment options. See related article by McNicholas et al., p. 1592 (7).
Diagnostic utility of allergy tests to predict baked egg and lightly cooked egg allergies compared to double‐blind placebo‐controlled food challenges
Authors: Marta Krawiec, Suzana Radulovic, Ru‐Xin Foong, Andreina Marques‐Mejias, Irene Bartha, Matthew Kwok, Zainab Jama, Faye Harrison, Cristian Ricci, Gideon Lack, George Du Toit, Alexandra F. Santos
Journal: Allergy (2023)

Abstract Background Double‐blind placebo‐controlled food challenges (DBPCFC) are the gold‐standard to diagnose food allergy. However, they can cause allergic reactions of unpredictable severity. We assessed accuracy of current and new diagnostic tests compared to DBPCFC to baked egg (BE) and to lightly cooked egg (LCE). Methods Children aged 6 months to 15 years were assessed for possible egg allergy as part of the BAT2 study (NCT03309488). They underwent clinical assessment, skin prick test (SPT), specific IgE (sIgE) and basophil activation test (BAT). The results of the tests were compared with DBPCFC outcomes to both BE and LCE. Results A total of 150 children underwent DBPCFC to BE, 60 (40%) reacted to and 85 (57%) tolerated BE and 5 (3%) had inconclusive oral food challenges (OFC). Seventy‐seven children tolerant to BE had DBPCFC to LCE and 16 reacted. The test within each modality with the best diagnostic performance for BE allergy was as follows: SPT to egg white (EW) (AUC = 0.726), sIgE to EW (AUC = 0.776) and BAT to egg (AUC = 0.783). BAT (AUC = 0.867) was the best test in the younger than 2 years age group. Applying 100% sensitivity and 100% specificity cut‐offs, followed by OFC, resulted in 100% diagnostic accuracy. BAT enabled the greatest reduction in OFC (41%). Using sIgE followed by BAT allowed to reduce the number of BATs performed by about 30% without significantly increasing the number of OFC. Conclusions The best diagnostic test was BAT to egg in terms of diagnostic accuracy and reduction in number of OFC. Using sIgE to EW followed by BAT required fewer BATs with sustained OFC reduction and diagnostic accuracy.
Absolute and Relative Risks of Kidney Outcomes Associated With Lithium vs Valproate Use in Sweden
Authors: Alessandro Bosi, Catherine M. Clase, Laura Ceriani, Arvid Sjölander, Edouard L. Fu, Björn Runesson, Zheng Chang, Mikael Landén, Rino Bellocco, Carl-Gustaf Elinder, Juan Jesus Carrero
Journal: JAMA Network Open (2023)

Importance Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy. Objective To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes. Design, Setting, and Participants This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden. Exposures New use of lithium vs new use of valproate and high (&amp;amp;gt;1.0 mmol/L) vs low serum lithium levels. Main Outcomes and Measures Progression of CKD (composite of &amp;amp;gt;30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users. Results The study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (&amp;amp;gt;1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76). Conclusions and Relevance In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.
Inpatient Hospitalization Costs Associated with Birth Defects Among Persons Aged &lt;65 Years — United States, 2019
Authors: Justin Swanson, Elizabeth C. Ailes, Janet D. Cragan, Scott D. Grosse, Jean Paul Tanner, Russell S. Kirby, Norman J. Waitzman, Jennita Reefhuis, Jason L. Salemi
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Changing treatments and medical costs necessitate updates to hospitalization cost estimates for birth defects. The 2019 National Inpatient Sample was used to estimate the service delivery costs of hospitalizations among patients aged <65 years for whom one or more birth defects were documented as discharge diagnoses. In 2019, the estimated cost of these birth defect-associated hospitalizations in the United States was $22.2 billion. Birth defect-associated hospitalizations bore disproportionately high costs, constituting 4.1% of all hospitalizations among persons aged <65 years and 7.7% of related inpatient medical costs. Updating estimates of hospitalization costs provides information about health care resource use associated with birth defects and the financial impact of birth defects across the life span and illustrates the need to determine the continued health care needs of persons born with birth defects to ensure optimal health for all.
Biodistribution and Internal Dosimetry of 68Ga-DOTA-IBA PET Imaging for Patients With Bone Metastases
Authors: Jian Yang, Jia Deng, Dongmei Fan, Gefei Chen, Zhonglin Lu, Hanxiang Liu, Greta S.P. Mok, Yue Chen
Journal: Clinical Nuclear Medicine (2023)

We have developed a new pharmaceutical, ibandronic acid (IBA), and preliminarily demonstrated that it is an efficient bisphosphonate for the diagnosis and treatment of bone metastases. This study aims to examine the biodistribution and internal dosimetry of the diagnostic 68 Ga-DOTA-IBA in patients.68 Ga-DOTA-IBA was intravenously injected based on 1.81-2.57 MBq/Kg into 8 patients with bone metastases. Each patient underwent 4 sequential static whole-body PET scans at 0.1, 0.45, 0.8, and 1.8 hours after injection. The acquisition time for each scan was 20 minutes with 10 bed positions. Image registrations and volume of interest delineation were first performed on Hermes, whereas percentage injected activity (%IA), absorbed dose, and effective dose were measured for source organs, using OLINDA/EXM v2.0. Dosimetrics for the bladder was based on a bladder voiding model.No adverse effects were observed on all patients. After the injection, 68 Ga-DOTA-IBA rapidly accumulated in bone metastases and cleared from nonbone tissues, as indicated by visual analysis and %IA measured on the sequential scans. High activity uptake was presented in the expected target organs, that is, bone, red marrow, and the drug-excretion organs such as kidneys and bladder. The mean total body effective dose is 0.022 ± 0.002 mSv/MBq.68 Ga-DOTA-IBA has high bone affinity and is promising in the diagnosis of bone metastases. Dosimetric results show that the absorbed doses for critical organs and total body are within the safety limit and with high bone retention. It also has the potential to be used in 177 Lu-therapy as a theranostic pair.
Mapping Health Disparities in 11 High-Income Nations
Authors: Neil J. MacKinnon, Vanessa Emery, Jennifer Waller, Brittany Ange, Preshit Ambade, Munira Gunja, Emma Watson
Journal: JAMA Network Open (2023)

Importance Health care delivery faces a myriad of challenges globally with well-documented health inequities based on geographic location. Yet, researchers and policy makers have a limited understanding of the frequency of geographic health disparities. Objective To describe geographic health disparities in 11 high-income countries. Design, Setting, and Participants In this survey study, we analyzed results from the 2020 Commonwealth Fund International Health Policy (IHP) Survey—a nationally representative, self-reported, and cross-sectional survey of adults from Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the UK, and the US. Eligible adults older than age 18 years were included by random sampling. Survey data were compared for the association of area type (rural or urban) with 10 health indicators across 3 domains: health status and socioeconomic risk factors, affordability of care, and access to care. Logistic regression was used to determine the associations between countries with area type for each factor, controlling for individuals’ age and sex. Main Outcomes and Measures The main outcomes were geographic health disparities as measured by differences in respondents living in urban and rural settings in 10 health indicators across 3 domains. Results There were 22 402 survey respondents (12 804 female [57.2%]), with a 14% to 49% response rate depending on the country. Across the 11 countries and 10 health indicators and 3 domains (health status and socioeconomic risk factors, affordability of care, access to care), there were 21 occurrences of geographic health disparities; 13 of those in which rural residence was a protective factor and 8 of those where rural residence was a risk factor. The mean (SD) number of geographic health disparities in the countries was 1.9 (1.7). The US had statistically significant geographic health disparities in 5 of 10 indicators, the most of any country, while Canada, Norway, and the Netherlands had no statistically significant geographic health disparities. The indicators with the most occurrences of geographic health disparities were in the access to care domain. Conclusions and Relevance In this survey study of 11 high-income nations, health disparities across 10 indicators were identified. Differences in number of disparities reported by country suggest that health policy and decision makers in the US should look to Canada, Norway, and the Netherlands to improve geographic-based health equity.
Randomized phase III trial of metabolic imaging-guided dose escalation of radio-chemotherapy in patients with newly diagnosed glioblastoma (SPECTRO GLIO trial)
Authors: Anne Laprie, Georges Noel, Leonor Chaltiel, Gilles Truc, Marie-Pierre Sunyach, Marie Charissoux, Nicolas Magne, Pierre Auberdiac, Julian Biau, Soléakhéna Ken, Fatima Tensaouti, Jonathan Khalifa, Ingrid Sidibe, Franck-Emmanuel Roux, Laure Vieillevigne, Isabelle Catalaa, Sergio Boetto, Emmanuelle Uro-Coste, Stéphane Supiot, Valérie Bernier, Thomas Filleron, Muriel Mounier, Muriel Poublanc, Pascale Olivier, Jean-Pierre Delord, Elizabeth Cohen-Jonathan-Moyal
Journal: Neuro-Oncology (2023)

Abstract Background Glioblastoma (GBM) systematically recurs after a standard 60 Gy radio-chemotherapy regimen. Since magnetic resonance spectroscopic imaging (MRSI) has been shown to predict the site of relapse, we analyzed the effect of MRSI-guided dose escalation on overall survival (OS) of patients with newly diagnosed GBM. Methods In this multicentric prospective phase III trial, patients who had undergone biopsy or surgery for a GBM were randomly assigned to a standard dose (SD) of 60 Gy or a high dose (HD) of 60 Gy with an additional simultaneous integrated boost totaling 72 Gy to MRSI metabolic abnormalities, the tumor bed and residual contrast enhancements. Temozolomide was administered concomitantly and maintained for 6 months thereafter. Results One hundred and eighty patients were included in the study between March 2011 and March 2018. After a median follow-up of 43.9 months (95% CI [42.5; 45.5]), median OS was 22.6 months (95% CI [18.9; 25.4]) versus 22.2 months (95% CI [18.3; 27.8]) for HD, and median progression-free survival was 8.6 (95% CI [6.8; 10.8]) versus 7.8 months (95% CI [6.3; 8.6]), in SD versus HD, respectively. No increase in toxicity rate was observed in the study arm. The pseudoprogression rate was similar across the SD (14.4%) and HD (16.7%) groups. For O(6)-methylguanine-DNA methyltransferase (MGMT) methylated patients, the median OS was 38 months (95% CI [23.2; NR]) for HD patients versus 28.5 months (95% CI [21.1; 35.7]) for SD patients. Conclusion The additional MRSI-guided irradiation dose totaling 72 Gy was well tolerated but did not improve OS in newly diagnosed GBM. Trial registration NCT01507506; registration date: December 20, 2011. https://clinicaltrials.gov/ct2/show/NCT01507506?cond=NCT01507506&amp;rank=1
Lymph node metastasis: An immunological burden
Authors: Amanda W. Lund
Journal: The Journal of Experimental Medicine (2023)

Lymph node metastasis in breast cancer depends in part on the acquisition of an IFN-dependent, MHC-II+ state that induces regulatory T cell expansion and local immune suppression (Lei et al. 2023. J. Exp. Med.https://doi.org/10.1084/jem.20221847).
A Case of Rectal Dissemination of Gastric Cancer Diagnosed by Simultaneous 18F-FDG PET/MRI
Authors: Feiya Zeng, Feibi Zeng, Naoki Sugiyama, Munenobu Nogami, Takamichi Murakami
Journal: Clinical Nuclear Medicine (2023)

Metastatic rectal cancer is rare and difficult to differentiate from primary rectal cancer. A 79-year-old man with a rectal mass detected by CT during postoperative follow-up of gastric cancer underwent 18 F-FDG PET/MRI. Fused PET/MRI images revealed a lower FDG uptake within the mass, which appeared to surround the outside of the rectum, than in the rectal wall, suggesting rectal dissemination of gastric cancer. PET/MRI was useful for differentiating between mass and rectal wall uptake, because of the high contrast resolution of MRI and precise image fusion made possible by simultaneous image acquisition.
<scp>Anti‐heat</scp> shock protein 10 <scp>IgG</scp> in chronic spontaneous urticaria: Relation with <scp>miRNA</scp>‐101‐5p and <scp>platelet‐activating</scp> factor
Authors: Bo Youn Choi, Eun‐Mi Yang, Hae‐Won Jung, Min‐Kyoung Shin, Junghyun Jo, Hyun‐Young Cha, Hae‐Sim Park, Ho‐Chul Kang, Young‐Min Ye
Journal: Allergy (2023)

Abstract Background Anti‐heat shock protein (HSP) autoantibodies are detected in autoimmune diseases. We sought to ascertain whether anti‐HSP10 IgG is present in patients with CSU and to elucidate the role of HSP10 in CSU pathogenesis. Method Using a human proteome microarray, six potential autoantibodies had higher expression in 10 CSU samples compared with 10 normal controls (NCs). Among them, HSP10 IgG autoantibody was quantified by immune dot‐blot assay in sera from 86 CSU patients and 44 NCs. The serum levels of HSP10 and microRNA‐101‐5p were measured in CSU patients and NCs. The effects of HSP10 and miR‐101‐5p on mast cell degranulation in response to IgE, compound 48/80, and platelet‐activating factor (PAF) were investigated. Results CSU patients had higher IgG positivity to HSP10 (40.7% vs. 11.4%, p = .001), lower serum HSP10 levels (5.8 ± 3.6 vs. 12.2 ± 6.6 pg/mL, p &lt; .001) than in NCs, and their urticaria severity was associated with anti‐HSP10 IgG positivity, while HSP10 levels were related to urticaria control status. MiR‐101‐5p was increased in CSU patients. PAF enhanced IL4 production in PBMCs from CSU patients. IL‐4 upregulated miR‐101‐5p and reduced HSP10 expression in keratinocytes. Transfection of miR‐101‐5p reduced HSP10 expression in keratinocytes. MiR‐101‐5p promoted PAF‐induced mast cell degranulation, while HSP10 specifically prevented it. Conclusion A new autoantibody, anti‐HSP10 IgG was detected in CSU patients, which showed a significant correlation with UAS7 scores. A decreased serum HSP10 level was associated with upregulation of miR‐101‐5p due to increased IL‐4 and PAF in CSU patients. Modulation of miR‐101‐5p and HSP10 may be a novel therapeutic approach for CSU.
Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma Recurrence at Penile Glans Masquerading Urinary Contamination on 18F-FDG PET/CT
Authors: Yue Zhang, Liqian Yu, Rang Wang, Minggang Su
Journal: Clinical Nuclear Medicine (2023)

Abstract A 69-year-old man with a history of extranodal NK/T-Cell lymphoma, nasal type (ENKTL-NT) performed an interim 18 F-FDG PET/CT for response evaluation. It showed an intense focal uptake at his penile glans, which was suspected as urinary contamination initially. However, he complained with redness and swelling of his penis during further history inquiry. After careful observation, the diagnosis of ENKTL-NT recurrence at penile glans was highly suspected. It was confirmed by percutaneous biopsy of the penile glans finally.